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A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neonatology".

Deadline for manuscript submissions: 25 August 2025 | Viewed by 11735

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Special Issue Editor

Dr. Simonetta Costa

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Guest Editor

1. Neonatology Unit, Policlinico Casilino, 00169 Rome, Italy
2. Department of Woman and Child Health and Public Health, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: neonatal intensive care; neonatal nutrition; necrotising enterocolitis; perinatal medicine

Special Issue Information

Dear Colleagues,

Preterm births are estimated to account for approximately 11% of all deliveries each year, and prematurity represents the leading worldwide cause of neonatal mortality and childhood mortality up to an age of five years. Despite advances in intensive neonatal care, the rates of neonatal morbidity remain high, calling for new care strategies to improve neonatal health outcomes.

Providing care for preterm infants requires 1) improving prenatal care, 2) devising new strategies to improve survival for periviable infants, 3) identifying care bundles aiming at reducing the risk of adverse outcomes for extremely low-gestational-age infants, 4) defining care guidelines for the growing population of late preterm infants and 5) offering palliative care pathways for treatable-but-not-curable pathologies.

To further the progress in preterm infants care, the application of translational medicine could offer new strategies for morbidity prevention and treatment, while the use of artificial intelligence could offer new diagnostic and monitoring tools.

This Special Issue of Children aims to collect the results of scientific research to help clinicians improve their care for preterm newborns. Therefore, we wish for a precious collaboration and look forward to receiving your contributions.

Dr. Simonetta Costa
Guest Editor

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Keywords

preterm infants
preterm birth
prenatal care
extremely low-gestational-age infants
periviable infants
late preterm infants
neonatal intensive care
palliative care
translational medicine
artificial intelligence
neonatal outcomes
prevention
care bundles

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Published Papers (9 papers)

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Research

16 pages, 745 KiB

Open AccessArticle

Immature Platelet Fraction as a Sensitive Biomarker in Neonatal Sepsis: Diagnostic Performance Preceding Thrombocytopenia

by Ilkay Er and Medeni Arpa

Children 2025, 12(7), 931; https://doi.org/10.3390/children12070931 - 15 Jul 2025

Viewed by 187

Abstract

Background: Early and accurate diagnosis of neonatal sepsis remains a clinical challenge due to nonspecific signs and limitations of conventional biomarkers. The immature platelet fraction (IPF), a novel hematologic parameter reflecting thrombopoietic activity, has emerged as a potential early sepsis indicator. This study aimed to evaluate the diagnostic value of IPF in neonatal sepsis prior to the onset of thrombocytopenia. Methods: This prospective study enrolled neonates with early-onset sepsis (EOS), late-onset sepsis (LOS), and healthy controls. IPF, C-reactive protein (CRP), procalcitonin (PCT), and hematologic indices were measured at diagnosis and 48–72 h post-treatment. Diagnostic performance was evaluated via ROC curve analysis, and correlations between IPF and inflammatory/hematologic markers were examined. IPF levels were also compared based on blood culture results. Results: IPF levels were significantly higher in both EOS (n: 56) and LOS (n: 50) groups compared to controls (n: 44) (p < 0.001). ROC analysis showed excellent diagnostic performance, with AUCs of 0.98 (EOS) and 0.99 (LOS). Following antibiotic treatment, IPF levels declined significantly (p < 0.001), supporting its dynamic value. Strong and moderate correlations were found with MPV and CRP, respectively, and an inverse association with platelet count, but not with PCT. Moreover, IPF levels were higher in culture-positive cases compared to culture-negative ones (13.1% vs. 9.8%; p = 0.017) and exhibited diagnostic performance comparable to CRP in predicting blood culture positivity. Conclusions: This study presents original and clinically relevant data supporting IPF as a promising and practical hematologic biomarker for early detection and treatment monitoring of neonatal sepsis. Its integration into standard sepsis evaluation protocols may improve early risk stratification and clinical decision-making in neonatal intensive care settings. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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12 pages, 756 KiB

Open AccessArticle

Continuous Renal Replacement Therapy in Critically-Ill Term and Preterm Newborns: A Single-Center Study in Belgrade

by Snezana Rsovac, Katarina Milosevic, Brankica Spasojevic, Mirjana Cvetkovic, Gordana Milosevski Lomic, Biljana Medjo, Mina G. Cobeljic, Nadja Vukasinovic, Vesna Selakovic, Dusan Todorovic, Masa Petrovic, Davor Plavec and Jasna Kalanj

Children 2025, 12(7), 828; https://doi.org/10.3390/children12070828 - 23 Jun 2025

Viewed by 340

Abstract

Background/Objectives: Continuous renal replacement therapy (CRRT) is an important treatment method that is becoming a commonly-used procedure in neonatal intensive care units (NICUs), especially in critically-ill neonates. Methods: We conducted a retrospective study aimed to evaluate factors influencing the outcomes of CRRT in neonates and preterm infants. The study analyzed data from 41 newborns treated with CRRT at our NICU over a ten-year period. Demographic, clinical, and laboratory parameters were assessed, including gestational age, birth weight, PRISM III score, and laboratory markers like urea, creatinine, and potassium levels, as well as characteristics of CRRT. Results: Our research found that the duration of CRRT, the presence of anuria, and higher potassium levels after initiation of CRRT were significant predictors of a poor outcome. Despite the lack of significant correlation between demographic characteristics, PRISM III score and the outcome, our findings highlight the importance of timely CRRT initiation and efficient management to improve survival. Conclusions: Our study identified several significant prognostic indicators in neonates undergoing renal replacement therapy. While these findings provide valuable insights, further research is needed to establish clear theoretical guidelines and improve clinical decision-making. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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12 pages, 821 KiB

Open AccessArticle

The Effect of the COVID-19 Pandemic and the Establishment of a Ronald McDonald House on Skin-to-Skin Times in the Neonatal Intensive Care Unit: A Retrospective Study

by Stephanie Schaible, Edda Hofstätter, Wanda Lauth and Martin Wald

Children 2025, 12(6), 803; https://doi.org/10.3390/children12060803 - 19 Jun 2025

Viewed by 381

Abstract

Objectives: Kangaroo care is vital for the development of premature and low-birthweight infants. However, detailed data on skin-to-skin times, especially for extremely preterm infants in NICUs, is lacking. This study quantifies skin-to-skin times for these infants at the neonatology department in Salzburg, considering factors like the COVID-19 pandemic, the opening of Ronald McDonald House, and sibling presence. Methods: We retrospectively analyzed data from the first eight weeks of life of 93 extremely preterm infants (<28 gestational weeks, <1500 g birth weight) treated at the Salzburg NICU from 2019 to 2023. Skin-to-skin times were recorded to the minute. Results: The mean value skin-to-skin time per visiting day was 241 min (±83), skin-to-skin was performed on 79.0% (±16.8) of the days of stay examined. During the pandemic, skin-to-skin care was performed on 64% of visit days, after the pandemic on 91% (p < 0.001). Before the Ronald McDonald House opened, the skin-to-skin time per visiting day was 215 min (±57.9), afterwards it was 273 min (±97) (p = 0.001). For Primipara the Kangaroo-Care time per day of visit was 257 min (±93), for Multipara 217 min (±52) (p = 0.043). Conclusions: Skin-to-skin is crucial for extremely premature infants and can be implemented for many hours a day. It is an integral part of parent-child interaction in a neonatal intensive care unit. External factors such as infrastructure, pandemic restrictions or siblings have a significant impact on skin-to-skin. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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10 pages, 204 KiB

Open AccessArticle

Second Attempt for Patent Ductus Arteriosus (PDA) Closure: Room for Acetaminophen? A Retrospective Single-Center Experience at Gaslini Children’s Hospital

by Samuele Caruggi, Andrea Calandrino, Gaia Cipresso, Marcella Battaglini, Paolo Massirio, Francesco Vinci, Irene Bonato, Chiara Andreato, Federica Mela, Lorenzo Curcio, Alessandro Parodi and Luca Antonio Ramenghi

Children 2025, 12(5), 577; https://doi.org/10.3390/children12050577 - 29 Apr 2025

Viewed by 528

Abstract

Background: The diagnosis of hemodynamically significant patent ductus arteriosus (hsPDA) occurs in 55% of very low birth weight (VLBW) preterm infants. There is no agreement on the best approach to ensure a quick hsPDA closure. Drug treatment of hsPDA fails in approximately 20% of cases with an increasing risk of prolonged ventilation, BPD, and NEC, as well as the need for surgical duct ligation. This study aims to highlight the efficacy of ibuprofen versus acetaminophen in the case of a second cycle of medical therapy after the failure of the first pharmacological approach for hsPDA closure. Methods: Every VLBW infant admitted to our NICU and treated for hsPDA was included in our retrospective research. Information about the clinical course, hsPDA diagnosis and treatment, and common complications associated with preterm birth was collected. A comparison was made between patients treated with acetaminophen or ibuprofen to assess effectiveness in hsPDA closing. Results: A total of 286 VLBW infants were included. First-course ibuprofen was effective in 87 of 115 infants (75.7%) treated, acetaminophen in 138 of 171 (80.7%). Second-course therapy with ibuprofen was effective in 62.5% of the patients, while acetaminophen was effective in 69.2%. No statistically significant difference was observed in the first-course and second-course success rates. Conclusions: This study confirms that acetaminophen is not inferior to ibuprofen in the closure of hsPDA in VLBW infants. Our data demonstrate that a second course of medical therapy after the failure of the first course could help close the majority of hsPDA cases without surgery. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

12 pages, 1373 KiB

Open AccessArticle

Analysis of Salivary Cytokines in Retinopathy of Prematurity

by Hwa-Shiu Wu, Hsin-Chun Huang and I-Lun Chen

Children 2025, 12(1), 80; https://doi.org/10.3390/children12010080 - 10 Jan 2025

Viewed by 774

Abstract

Background/Objectives: This cohort study aimed to establish a correlation between salivary cytokines and retinopathy of prematurity (ROP) in premature neonates. Additionally, we sought to identify a minimally invasive method for cytokine detection in this population. Methods: We recruited premature neonates born at less than 34 weeks gestational age (GA), with no history of maternal or neonatal infections. Salivary samples were collected on their first (D1) and seventh (D7) days of life, and cytokine levels were measured using the MILLPLEXMAP Human multiplex assay. Results: A total of 125 neonates were included in the study, categorized into two groups based on the severity of ROP: None to Mild and Moderate to Severe. The salivary levels of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α on D1 and D7 were significantly higher in the Moderate to Severe ROP group compared to the None to Mild ROP group (p = 0.005, 0.004, 0.026, 0.018, 0.001, 0.007, 0.025, and 0.002, respectively). After adjusting for GA, the levels of IL-6 and VEGF on D7 were significantly elevated in the Moderate to Severe ROP group compared to the None to Mild ROP group (p = 0.024 and 0.016, respectively). Conclusions: This study establishes a novel, non-invasive method for the early prediction of ROP in premature neonates by correlating salivary cytokine levels in early life with the subsequent development of ROP. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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11 pages, 3317 KiB

Open AccessArticle

Reimagining Kangaroo Care for Preterm Infants: A Novel Garment for Safe and Comfortable Bonding

by Alexandra McMillin, Aviva Presser Aiden, Jules P. Sherman, Ruth Ann Crystal and William D. Rhine

Children 2024, 11(11), 1392; https://doi.org/10.3390/children11111392 - 16 Nov 2024

Viewed by 2234

Abstract

Background/Objectives: Kangaroo Care (KC) has been proven to enhance physiological stability, growth, and bonding in preterm, low-birthweight infants. Despite its benefits, KC is underutilized in Level IV Neonatal Intensive Care Units (NICUs) due to challenges in managing medical equipment. This study introduces the Kangarobe™, a novel garment designed to facilitate safe, comfortable, and efficient KC for medically fragile infants in high-acuity NICUs. Methods: From 2021 to 2023, a feasibility study was conducted involving 25 infant-parent dyads in a Level IV NICU. The Kangarobe™ was designed using human-centered design principles and tested on infants dependent on respiratory support. Surveys employing a 5-point Likert scale were administered to parents and nursing staff to assess safety, comfort, ease of use, and procedural access. Results: Survey results showed positive feedback from both parents and nursing staff, particularly in the areas of safety and comfort. For example, 72–80% of parents and nurses responded positively regarding ease and comfort. High level of agreement (76%) on the security of medical line management, with minimal negative feedback. In addition, parents using the Kangarobe™ held their infants for an average of 171 min per session, with a notable increase compared to the typical 75 min, indicating enhanced comfort and feasibility for extended KC sessions. The Kangarobe™ successfully enabled the secure management of medical lines and tubes, with the vertical access window improving procedural efficiency without interrupting KC. Conclusions: The Kangarobe™ demonstrates promise in addressing barriers to KC in high-acuity NICUs. By enhancing safety, comfort, and ease of use, it supports wider adoption of KC practices, potentially improving patient safety, staff efficiency, and family-centered care. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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10 pages, 280 KiB

Open AccessArticle

Do Different Amounts of Exogenous Surfactant Differently Influence Cerebrovascular Instability in a Consecutive Group of Preterm Babies? Preliminary Results from a Single-Center Experience

by Andrea Calandrino, Samuele Caruggi, Francesco Vinci, Marcella Battaglini, Paolo Massirio, Gaia Cipresso, Chiara Andreato, Giorgia Brigati, Alessandro Parodi, Giulia Polleri, Diego Minghetti and Luca Antonio Ramenghi

Children 2024, 11(9), 1088; https://doi.org/10.3390/children11091088 - 5 Sep 2024

Viewed by 940

Abstract

Background: Thirty years ago, the first attempt by Saliba and colleagues was made to reduce the negative effects (hypercarbia) of exogenous surfactant (ES) by slowing its administration. Sixteen years later, we observed the first less invasive surfactant administration (LISA) attempt by Kribs and colleagues. Many studies, since that time, have tried to minimize the invasiveness of ES and subsequent cerebral blood flow perturbations through studies using near-infrared spectroscopy (NIRS). We sought to address this medical challenge by identifying a less problematic modality of ES administration by delivering multiple aliquots of ES instead of a single one, as typically performed. The aim of this study was to test the hypothesis that a different way of administering ES using more aliquots could be a safe alternative that should be assessed in further studies. Methods: Patients between 26 + 0 and 35 + 6 weeks of gestational age (GA) requiring ES administration were enrolled (April 2023–February 2024). Differently fractioned doses were delivered according to an arbitrary standard dosage (0.3 mL per aliquot in babies < 29 weeks; 0.6 mL in babies ≥ 29 weeks), while NIRS and transcutaneous CO₂ (tCO₂) monitoring were always performed. ES’s effectiveness was assessed based on the reduction in the Oxygen Saturation Index (OSI) after administration. Persistent desaturation, bradycardia, and airway obstruction were defined as adverse effects and used to evaluate safety during ES administration, as well as variability in NIRS-rSO₂ values and tCO₂. Results: Twenty-four patients were enrolled with a median GA of 29 weeks (IQR 4.5) and BW of 1223 ± 560 g. In addition, 50% of the cohort received fewer than three aliquots, whereas the other 50% received more than three. Monitoring was started before the procedure and continued 30′ after the last ES aliquot administration. The variability in NIRS-SpO₂ values was significantly higher in the group (p = 0.007) with a lower number of aliquots administered. Similarly, increased NIRS-rSO₂ values (p = 0.003) and increased tCO₂ levels (p = 0.005) were observed in infants who underwent an ES split after the administration of a low number of aliquots. Conclusions: Our data obtained from the group with > 3 fractionated doses of ES seem to justify the preparation of a more robust study, as the combination of reduced NIRS variability and reduced tCO₂ maximum levels is consistent with more stable cerebral blood flow during the challenging time of ES administration. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

13 pages, 4299 KiB

Open AccessArticle

Use of N-Acetylcysteine in Preterm Neonates with Enteral Feeding Intolerance and Intestinal Obstruction: A Case Series and Review of the Literature

by Domenico Umberto De Rose, Francesca Landolfo, Flaminia Pugnaloni, Paola Giliberti, Alessandra Santisi, Claudia Columbo, Ludovica Martini, Maria Paola Ronchetti, Paolo Maria Schingo, Guglielmo Salvatori, Fabio Fusaro, Pietro Bagolan, Andrea Dotta, Irma Capolupo and Andrea Conforti

Children 2024, 11(7), 873; https://doi.org/10.3390/children11070873 - 18 Jul 2024

Viewed by 3567

Abstract

(1) Background: The use of N-acetylcysteine (NAC) to relieve meconium obstruction of prematurity in the first days of life has been reported, with NAC reducing the viscosity of luminal contents by cleaving the disulfide bonds of mucoproteins. However, its use in this population should be further explored since it has been associated with hypernatremia and transient increase in transaminases and bilirubin. (2) Methods: In this retrospective study, we included neonates admitted because of enteral feeding intolerance and intestinal obstruction from 2019 to 2021 who received NAC as a rescue therapy before explorative laparotomy. (3) Results: We summarized the clinical presentation of six preterm neonates with enteral feeding intolerance and intestinal obstruction who received NAC as a rescue therapy. Four infants (66.7%) gradually improved without the need for explorative laparotomy, whereas two infants (33.3%) underwent the creation of an ileostomy. No cases of hypernatremia or hepatic derangement associated with NAC therapy were observed. (4) Conclusions: We described the use of NAC treatment by nasogastric tube and/or rectal enemas in preterm infants with enteral feeding intolerance and intestinal obstruction after a multidisciplinary assessment, but the limited sample size did not allow us to obtain definitive conclusions and further research is needed in this field, given the limited evidence about NAC treatment in preterm infants. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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9 pages, 995 KiB

Open AccessCommunication

Premature Babies Can Be Cared for in the Maternity Ward without an Increased Risk and Discharged with a Feeding Tube If Necessary

by Lea Rösch, Edda Hofstätter, Franziska Krasnitzer-Leitner and Martin Wald

Children 2024, 11(4), 456; https://doi.org/10.3390/children11040456 - 10 Apr 2024

Cited by 1 | Viewed by 1840

Abstract

In general, premature babies are discharged home when they reach full self-feeding. We established a discharge management protocol which allows for discharging late preterm babies with a feeding tube if necessary. This retrospective study included 108 preterm infants (34+ weeks) born in 2019 and 2020. The preterm infants discharged with a feeding tube (n = 32) were born at 35.23 weeks’ gestation (±0.884), with a birth weight of 2423 g (±375.1), and were discharged at 7.22 days (±3.63) and had a weight of 3466 g (±591.3) at the first outpatient visit around the expected birth date. The preterm infants discharged without a feeding tube were born at 35.97 weeks’ gestation (±0.702) with a birth weight of 2589 g (±424.84), discharged home at 6.82 days (±7.11) and a weight of 3784 g (±621.8) at the first outpatient visit. The gestational week and birth weight were statistically significantly different between the groups, with a p-value of <0.001 for each, and the length of hospital stay (p = 0.762) and weight at follow-up (p = 0.064) did not significantly differ. No infant required tube-feeding at the time of the first outpatient visit, i.e., the time of expected birth. Therefore, with well-thought-out management, it is possible and safe to discharge preterm infants home with a feeding tube. Full article

(This article belongs to the Special Issue Providing Care for Preterm Infants)

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